Are Bispecific Antibodies Considered Chemotherapy for DLBCL?

No, bispecific antibodies are not considered traditional chemotherapy. They belong to a distinct class of treatments called targeted immunotherapy. Instead of using chemicals that broadly affect rapidly dividing cells, bispecific antibodies work by redirecting and activating your body’s existing immune system to identify and destroy the lymphoma cells ^[1].

How Bispecific Antibodies Work

The term “bispecific” means that these engineered immune proteins have two distinct “arms,” allowing them to grab onto two different targets at the exact same time:

• Arm 1 (The Cancer Target): One arm reaches out and grabs a specific protein on the surface of your diffuse large B-cell lymphoma (DLBCL) cells. For drugs currently used in DLBCL, this target is typically a protein called CD20 ^[2].
• Arm 2 (The Immune Target): The other arm reaches out and grabs a protein called CD3, which is found on your healthy T-cells (a type of white blood cell that fights infection and disease) ^[2][3].

By grabbing both cells simultaneously, the bispecific antibody acts as a physical bridge. It pulls the healthy T-cell directly into contact with the lymphoma cell ^[3]. This forced close contact triggers the T-cell to activate and release toxic substances that destroy the cancer cell ^[2].

How This Differs From Cytotoxic Chemotherapy

Traditional cytotoxic chemotherapy uses drugs with various mechanisms that preferentially affect rapidly dividing cells throughout the body. Because chemotherapy cannot easily distinguish between a cancer cell and a healthy dividing cell, it often leads to widespread side effects like hair loss and mouth sores. The success of chemotherapy relies on the drugs’ chemical ability to damage the cancer cells.

Bispecific antibodies, such as epcoritamab and glofitamab, represent a completely different approach from the chemotherapy you may have previously received. Their cancer-killing power depends on the presence of the CD20 target on the lymphoma and the availability and activity of your immune system’s T-cells ^[4]. In clinical studies of heavily pretreated patients—including some who had previously received CAR-T cell therapy—these drugs have produced deep responses for some patients, offering an alternative when chemotherapy is no longer effective ^[5].

Important Differences in Side Effects and Administration

While bispecific antibodies do not usually cause the exact same pattern of side effects as chemotherapy, they are not side-effect free. They can still cause overlapping toxicities like low blood counts, fatigue, nausea, and an increased risk of serious infections. Furthermore, because they rapidly activate your immune system, they carry unique and potentially severe risks that require careful monitoring ^[6]:

• Cytokine Release Syndrome (CRS): A systemic inflammatory response that can cause high fevers, chills, rapid heartbeat, low oxygen, and dangerous changes in blood pressure.
• Neurologic Toxicity (ICANS): Immune-related side effects that can cause confusion, difficulty speaking, severe sleepiness, weakness, or seizures.

Because of these risks, these drugs are given using a “step-up” dosing schedule, meaning the dose is slowly increased over time to allow your body to adjust. Epcoritamab is given as an injection under the skin, while glofitamab is given as an intravenous (IV) infusion. Both require careful monitoring, premedication, and sometimes hospitalization during the earliest doses.

When to Seek Immediate Medical Help:
If you are receiving a bispecific antibody, you must contact your treatment team immediately or seek emergency care if you experience any signs of CRS or neurologic toxicity, such as:

• Persistent fever or chills
• Difficulty breathing or dizziness
• Confusion, trouble speaking, or unusual sleepiness